Interleukin-1 (I1-1) is a low molecular weight peptide synthesized by several different cell types including macrophages. Il-1 has wide range of biological effects, including the induction of the synthesis of inflammatory substances, acute phase reactants, and fever. A great deal of work has recently been done which shows that I1-1 is involved in the activation of peripheral T-cells in immune responses. However, I1-1 was originally described as an activator of thymocytes, and this activity has been the basis for the assay of I1-1. Several laboratories, including my own, have recently shown that the development of the fetal thymus can be studied using a murine fetal thymus organ culture system. Organ culture methodology offers the opportunity to study thymus development in vitro using a closed system in which the parameters involved in the development of the thymus can be easily controlled. I have recently shown that the differentiation of thymocytes is likely to involve cellular interaction between thymocyte progenitors and non-lymphoid cells in the thymus which bear the class II major histocompatibility antigen Ia. Antibodies against Ia will inhibit the growth of thymocytes in fetal thymus organ cultures. However, the addition of exogenous I1-1 to the cultures will reverse the inhibitory effects of anti-Ia. I have also shown that the addition of antibodies to I1-1 will inhibit the development of thymocytes in organ cultures. These results, taken together, imply a role for I1-1 in the differentiation of thymocytes in the fetal thymus. The goal of this study is to determine the mechanism by which I1-1 mediates the cellular interactions which are involved in thymocyte development. I believe that the fetal thymus organ culture system may provide a model system for the study of I1-1 effects which may be applicable to other cellular systems as well.